BNIP3 Is Implicated In Oligodendrocyte Cell Apoptosis Following Carbon Monoxide Poisoning

To investigate the role of B cell lymphoma/lewkmia-2 and adenovirus E1B19 000 interacting protein 3(BNIP3)in oligodendrocyte cell apoptosis induced by carbon monoxide poisoning(CO poisoning)and the potential signal pathways correspondingly.Forty male C57 BL/6 mice were randomly divided into the control group and CO poisoning group.Mice were left to breathe room air(control group)or subjected to 40 min exposure to 2 500-3 000 ppm CO(CO poisoning group).The mice were sacrificed at 1,3,7 d and 14 d following CO poisoning.We examined the damage of myelin sheath and oligodendrocytes by observing the expression of myelin basic protein(MBP)and oligodendrocyte transcription factor2(Olig2)in corpus callosum.Tunel related detection and transmission electron microscope were used to identify apoptosis of oligodendrocyte.Furthermore,we explored the role of BNIP3 and potential signal pathways in the oligodendrocyte cell death following CO poisoning by observing the expression of BNIP3,Bcl-2 Associated X Protein(Bax)and cysteinyl aspartate specific proteinase 9(caspase 9).Immunohistochemistry(IHC)showed that the expression of MBP decreased significantly in the corpus callosum from 1 d(P<0.05)to 7 d(P<0.01)and increased from 7 d to 14 d(P<0.05)in some degree after CO poisoning compared with the control group of MBP and that Olig2 expression increased markedly in 3 d(P<0.01)CO poisoning group compared with the control group of Olig2.The results of MBP and Olig2 in western blot revealed that MBP began to decrease from 1 d(P<0.01)to 7 d(P<0.01)and increased in 14 d(P<0.01)compared with the control group of MBP,and that Olig2 increased obviously in 3 d(P < 0.01)compared with the control group of Olig2.Tunelrelated detection revealed that percentage of positive cells began to increase from 1 d(P<0.01)to 7 d(P<0.01)and increased in 14 d(P<0.01)compared with the control group in corpus callosum.The apoptosis of oligodendrocyte was discovered by transmission electron microscope in corpus callosum.Western blot analysis showed that the levels of BNIP3 were increased in 1 d(P<0.01)respectively,started to decrease in 3 d(P<0.01)and finally recovered in 14 d(P>0.05),as compared with the control group of BNIP3.Moreover,compared with the control group of Bax,Bax was also upregulated in the corpus callosum from 1 d(P<0.01)to 7 d(P<0.05)after CO poisoning.The expression of Caspase9 showed the similar tendency that increased in 1 d(P<0.01),decreased in 3 d(P<0.01)and recovered in 7 d(P>0.05)compared with the control group of caspase9.BNIP3 expression was correlated with the Bax(P<0.01)and caspase9(P<0.01).BNIP3 may play an important role in the apoptosis of oligodendrocytes induced by CO poisoning via the pathway of caspase dependent mitochondria apoptosis.